Doxorubicin

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== Information about Doxorubicin ==  Doxorubicin, epirubicin, idarubicin and valrubicin are structurally related cytotoxic antineoplastic antibiotics used in the therapy of several forms of lymphoma, leukemia, sarcoma and solid organ cancers.  Doxorubicin is associated with a high rate of transient serum enzyme during therapy and to rare instances of clinically apparent acute liver injury with jaundice that can be severe and even fatal.  Epirubicin and idarubicin have similar profiles of activity and adverse events as doxorubicin, but have been less commonly used and their potential for causing liver injury has been less well defined.  Valrubicin is instilled directly in the bladder as treatment of refractory urinary bladder cancer, has little systemic distribution, and has not been associated with serum enzyme elevations or clinically apparent liver injury.   

Liver safety of Doxorubicin

Mechanism of action of Doxorubicin

  Doxorubicin (dox” oh roo’ bi sin), epirubicin (ep” i roo’ bi sin), idarubicin (eye” da roo’ bi sin) and valrubicin (val roo' bi sin) are cytotoxic, anthracycline antibiotics which are believed to act by intercalating between DNA base pairs and uncoiling the DNA helix, which results in inhibition of DNA synthesis and the normal DNA breaking and resealing action of DNA toposiomerase II.  These actions lead to apoptosis of rapidly dividing cells.  These four agents are all semisynthetic derivatives of daunorubicin and share activities and toxicities.  All four agents have severe adverse events particularly myelosuppression that can lead to severe neutropenia and sepsis.  These agents should be administered only under the supervision of physicians who are experienced in the use of cancer chemotherapeutic agents and in managing their side effects

The greatest clinical experience has been with doxorubicin which was previously known as adriamycin.  Doxorubicin has potent activity in several forms of cancer, including acute leukemia, lymphomas, sarcomas and solid tumors.  Doxorubicin was approved for use in the United States in 1974, and it remains an important agent in many cancer chemotherapeutic regimens. 

Indications / clinical use for Doxorubicin

Current indications include treatment of bladder, breast, lung, ovarian stomach and thyroid cancers, Hodgkin disease, acute lymphocytic and non-lymphocytic leukemia, Wilm tumor, neuroblastoma and sarcomas

Dosage and administration for Doxorubicin

Doxorubicin is available as a powder for injection and in liquid solution in 10, 20, 50, 100, 150 and 200 mg vials [2 mg/mL] generically and under the brand name Adriamycin.  Liposomal formulations are also available.  Doxorubicin is typically given intravenously in doses of 60 to 75 mg per meter squared2 body surface area every 21 to 28 days.  The dosage varies by indication, body surface area and hepatic function. 

Side effects of Doxorubicin

Common side effects include bone marrow suppression, nausea, vomiting, mucositis, diarrhea, headache, dizziness, confusion, neuropathy, alopecia, skin rash and fever.  High doses or prolonged therapy with doxorubicin can cause serious cardiac toxicity which is a major dose limiting side effect.  Local extravasation of doxorubicin causes severe local tissue injury.  Long term folllow up studies of treated patients suggest that secondary malignancies may arise more frequently in those who receive high, total accumulative doses of doxorubicin. 


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